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CAR T-Cell Therapy in Refractory B-Cell Lymphomas


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Stephen J. Schuster, MD

Stephen J. Schuster, MD

As reported at the 2017 American Society of Hematology Annual Meeting & Exposition and in The New England Journal of Medicine, Stephen J. Schuster, MD, of the Perelman School of Medicine at the University of Pennsylvania, and colleagues found that chimeric antigen receptor (CAR) T-cell therapy produced responses in a high proportion of patients with B-cell lymphomas refractory to or who had relapsed after previous treatments.

 

This case-series study was conducted at the Hospital of the University of Pennsylvania and included 14 adult patients with diffuse large B-cell lymphoma and 14 patients with follicular lymphoma treated between March 2014 and August 2016. Outcome data are current through May 2017. Patients received an infusion of autologous T cells expressing a CD19-directed CAR (CTL019; 1.00 × 108 to 5.00 × 108 CTL019 cells) at 1 to 4 days after completion of lymphodepleting chemotherapy.

Response Rates

Among the 28 patients, response was observed in 18 (64%), including 7 (50%) with diffuse large B-cell lymphoma and 11 (79%) with follicular lymphoma. Complete remission was observed in 6 patients (43%) with diffuse large B-cell lymphoma and 10 patients (71%) with follicular lymphoma.

CTL019 cells were found to proliferate in vivo and were detectable in blood and bone marrow of both responders and nonresponders. At a median follow-up of 28.6 months, 86% of responders with diffuse large B-cell lymphoma and 89% of responders with follicular lymphoma had a maintained response. All patients achieving complete remission by 6 months remained in remission at 7.7 to 37.9 months (median = 29.3 months) after induction. There was a sustained reappearance of B cells in 8 of 16 patients and improvement in immunoglobulin (Ig) G levels in 4 of 10 patients and IgM levels in 6 of 10 patients at ≥ 6 months and in IgA levels in 3 of 10 patients at ≥ 18 months.

Adverse Events

Severe cytokine-release syndrome occurred in five patients (18%), with no deaths observed. Eleven patients (39%) had treatment-related neurologic toxic effects. Serious encephalopathy occurred in three patients (11%), with two being self-limiting and one being fatal.

The investigators concluded: “CTL019 cells can be effective in the treatment of relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. High rates of durable remission were observed, with recovery of B cells and immunoglobulins in some patients. Transient encephalopathy developed in approximately one in three patients and severe cytokine-release syndrome developed in one in five patients.” ■

Schuster SJ, et al: N Engl J Med 377:2545-2554, 2017.


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